In recent years we have developed many spontaneously metastasizing rat mammary carcinomas with varying degrees of virulence. These tumors shed soluble, organ-specific antigen in rough proportion to their metastasizing capacity. Such antigen can be detected in the sera of rats as early as one week after receiving the tumor implantation, even before the graft is palpable, and its level increases as the tumor grows. Syngeneic antibodies against this antigen cannot be raised in W/Fu rats, as is the case in man with such tumor-associated antigens. Utilizing this tumor system, we plan to study the mechanisms of action of this soluble cell surface antigen on the host immune system, especially the function of T- and B-lymphocytes, macrophages, and natural killer cells, both in syngeneic rats and in athymic nude mice which reject these metastasizing tumors. An attempt will also be made to learn the biochemical mechanisms of tumor cell invasiveness, antigen shedding, and metastasis by studying the activity of lysosomal enzymes, plasma membrane marker enzymes and glycosyltransferases in these tumors.